tbuckley/cabot-search huggingface dataset:
Model for Integration of Monogenic Diabetes Diagnosis Into Routine Care: The Personalized Diabetes Medicine Program
Authors: Haichen Zhang, Jeffrey W. Kleinberger, Kristin A. Maloney, Yue Guan, Trevor J. Mathias, Katharine Bisordi, Elizabeth A. Streeten, Kristina Blessing, Mallory N. Snyder, Lee A. Bromberger, Jessica Goehringer, Amy Kimball, Coleen M. Damcott, Casey O. Taylor, Michaela Nicholson, Devon Nwaba, Kathleen Palmer, Danielle Sewell, Nicholas Ambulos, Linda J.B. Jeng, Alan R. Shuldiner, Philip Levin, David J. Carey, Toni I. Pollin
Journal: Diabetes Care (2022)

To implement, disseminate, and evaluate a sustainable method for identifying, diagnosing, and promoting individualized therapy for monogenic diabetes.Patients were recruited into the implementation study through a screening questionnaire completed in the waiting room or through the patient portal, physician recognition, or self-referral. Patients suspected of having monogenic diabetes based on the processing of their questionnaire and other data through an algorithm underwent next-generation sequencing for 40 genes implicated in monogenic diabetes and related conditions.Three hundred thirteen probands with suspected monogenic diabetes (but most diagnosed with type 2 diabetes) were enrolled from October 2014 to January 2019. Sequencing identified 38 individuals with monogenic diabetes, with most variants found in GCK or HNF1A. Positivity rates for ascertainment methods were 3.1% for clinic screening, 5.3% for electronic health record portal screening, 16.5% for physician recognition, and 32.4% for self-referral. The algorithmic criterion of non-type 1 diabetes before age 30 years had an overall positivity rate of 15.0%.We successfully modeled the efficient incorporation of monogenic diabetes diagnosis into the diabetes care setting, using multiple strategies to screen and identify a subpopulation with a 12.1% prevalence of monogenic diabetes by molecular testing. Self-referral was particularly efficient (32% prevalence), suggesting that educating the lay public in addition to clinicians may be the most effective way to increase the diagnosis rate in monogenic diabetes. Scaling up this model will assure access to diagnosis and customized treatment among those with monogenic diabetes and, more broadly, access to personalized medicine across disease areas.
AB0829 Body composition in spondyloarthritis: is there any impact on disease activity?
Authors: F. Chennouf, H. Azzouzi, H. Boutaibi, I. Linda
Journal: Annals of the Rheumatic Diseases (2022)

Background The relationship between obesity and inflammation is bidirectional. Thus, obesity may influence clinical response to biological treatment. Objectives To investigate the association of obesity and body composition with disease activity in patients with spondyloarthritis (SA). Methods This is a cross-sectional study designed on spondyloarthritis patients diagnosed according to ASAS 2009 classification. Bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAS), Bath ankylosing spondylitis functional index (BASFI), and Bath ankylosing spondylitis metrology index (BASMI) were assessed. Obesity was evaluated clinically by body mass index (BMI) and waist circumference (WC). Total body composition, total and regional fat and lean mass, android/gynoid ratio (A/G), fat mass index (FMI), fat-free mass index (FFMI) were measured by dual-energy X-ray absorptiometry (DXA) and reported as absolute values. Blood samples were collected to determine C-reactive protein serum (CRP) levels for each patient. Socio-demographic data, comorbidities, physical activity, disease-related variables (duration, characteristics, and drugs) were also collected. Correlations and regressions were made by SPSS.20. Results Forty-four SA participants (65.9% male) were enrolled. Their mean age was 39.82 ± 14.20 years and the mean ASDAS CRP was 1.42 ± 0.86. Patients under biologic disease-modifying antirheumatic drugs (bDMARDs) showed lower FMI (p = 0.011), percentage of fat mass (p = 0.008), and gynoid fat mass (p = 0.01). Correlations between ASDAS using CRP, total body fat mass, FMI, FFMI, visceral adipose tissue (VAT), appendicular lean height, and the A/G ratio were not statistically significant. Nevertheless, ASDAS CRP was positively correlated to total body mass (r = 0.352; p = 0.019), gynoid fat mass (r = 0.329, p = 0.029), and android fat mass (r = 0.323, p = 0.032). The association of disease activity and gynoid fat mass persisted after adjustment on disease duration and age (ß = 0.355, 95%IC [0.00003; 0.0003], p = 0.021). Conclusion Gynoid and android fat mass affected disease activity in our SA patients. However, FMI, visceral fat, and skeletal muscle mass showed no significant association with disease activity. Disclosure of Interests None declared
AB1556-HPR IDENTIFYING BARRIERS IN EARLY RECOGNITION AND MANAGEMENT OF PATIENTS WITH AXIAL SPONDYLOARTHRITIS: A RETROSPECTIVE REVIEW
Authors: A. Nandagudi, M. Dare, D. Laila, A. Bharadwaj
Journal: Annals of the Rheumatic Diseases (2022)

Background Axial spondyloarthritis are immune and genetically mediated inflammatory arthritis where there is significant delay in diagnosis and management of roughly 8.5 years; leading to poorer outcome and quality of life for a patient. Objectives This aim of audit was to improve the identification and referral pathways for patients with axial spondyloarthritis in South West Essex United Kingdom as per agreed NICE &amp; EULAR criteria. Methods This was a retrospective audit of 35 patients diagnosed as Axial Spondyloarthritis in secondary care and those which was referred to secondary care by community triage MSK service (Connect) as Axial Spondyloarthritis, between January 2019 and March 2020. Data was extracted to look at demographics, diagnostic investigations performed, duration from symptom onset to diagnosis and the patient journey to secondary care. Results Out of total 35 patients, 63% were males with a median age of 35 years. Of all the GP referrals 17% were directly to secondary care and 71% were via triage service. Twelve percent of referrals came from other specialties. The average timeframe from symptoms onset to referral by GP was 7.7 years. Average time before a patient was seen by a rheumatologist after referral was 4.4 months. After evaluation in clinic, 30 cases (85.7%) were finally diagnosed as AxSpA after rheumatologist’s review. Rest were mechanical back pain. Inflammatory back pain was mentioned in 18% of referrals by GP and 80% of referrals letters by triage service. Base line investigations included: CRP was in 39% of cases under GP care and 100% cases under triage service. Additionally, HLAB27, X ray and MRI tests were done in 22%, 17% and 22% of GP cases respectively and 86%, 80% and 80% of cases from triage service. After specialist review, HLAB27 was positive in 49% of patients, X ray positive sacroileitis in 54.5% patients and rest had MRI positive sacroileitis and spinal features. Some had both X ray and MRI investigations. Conclusion Lack of education and awareness about spondyloarthropathy remains the most prominent factor behind delay to diagnosis. Lack of important information and clinical features on referral letters are also a contributing factor. It is evident that early referral to rheumatologist care and early triaging during reviews are crucial to diagnose AxSpA. We are piloting use of SPADE tool in suspected AxSpA cases to guide clinical reasoning and early referrral. Disclosure of Interests None declared
AB0814 ASSOCIATION BETWEEN UVEITIS AND OTHER CLINICAL MANIFESTATIONS OF ANKYLOSING SPONDYLITIS
Authors: A. Godzenko, I. Razumova, M. Godzenko
Journal: Annals of the Rheumatic Diseases (2022)

Background Uveitis is a frequent extra-skeletal manifestation of ankylosing spondylitis (AS). Data on the association of uveitis with other clinical manifestations of AS are contradictory and require further study. Objectives To assess the association of uveitis in AS with demographics and genetics, spine lesions, peripheral disease, coxitis, enthesitis. Methods 402 AS pts (New York criteria, 1984), were observed in V.A. Nasonova Research Institute of Rheumatology. 168 pts had at least 1 episode of uveitis (group 1), 234 pts did not have uveitis (group 2). The patients underwent standard clinical, laboratory and instrumental examination, including HLA-27- testing, Х-ray examinaiton of joints and spine, ultrasonography of joints and entheses. Two groups were compared by gender, onset age and AS duration, presence of HLA-B27, damage of the spine, hip and peripheral joints and enthesitis. Results Both groups were dominated by men: 117 of 168 in group 1 and 189 of 234 in group 2. However, among patients with uveitis, the proportion of women was significantly higher: 51/168 (30.3%) and 45/234 (19.2%), p=0.01. The average duration of the disease was comparable in both groups – 14.9±10.2 and 12.8±9.9 years, respectively. The number of patients with AS onset before the age of 16 also did not significantly differ: 22/168 (13.1%) in the group with uveitis, 35/234 (14.9%) in the group without uveitis, p=0.6. HLA-B27 in the group with uveitis was in 166/168 patients (98.8%) and in 221/234 (94.4%) in the group without uveitis, p=0.04. Syndesmophytes were observed in both groups with similar frequency: in the cervical spine - in 49/168 (29.1%) in group 1 and in 78/234 (33.3%) in group 2, p&gt;0.05; in the lumbar spine – in 87 /168 (51.8%) and in 139/234 (59.4%), respectively, p&gt;0.05. Hip joint lesion (coxitis) was present in 75/168 (44.6%) and in 112/234 (53.8%) respectively, p=0.52; enthesitis – in 114/168 (67,9%) and in 168/234(71,8%), p&gt;0.05. Peripheral arthritis was observed significantly more often in the group with uveitis: in 113/168 (67.2%) and in 70/234 (33.2%) respectively, p&lt;0.001; its predominant localization was knee - 71/113 (62.8%) and ankle - 54/113 (47.8%). Conclusion AS with uveitis is characterized by a greater proportion of women and stronger association with HLA-B27, compared with patients without uveitis. Peripheral arthritis with predominant involvement of the knee and ankle joints is significantly more common in AS pts with uveitis compared with pts without uveitis. References [1]Lee JH, Choi M, Rim THT, Lee SC, Lee CS. Clinical Characteristics and Prognostic Factors in Ankylosing Spondylitis Associated Uveitis.Ocul Immunol Inflamm. 2019;27(1):64-69. doi: 10.1080/09273948.2017.1359630. Disclosure of Interests None declared
AB0014 THE ROLE OF NLRP3 INFLAMMASOME POLYMORPHISMS IN THE GOUT SUSCEPTIBILITY
Authors: D. Clavijo-Cornejo, A. López-Reyes, E. Cruz-Arenas, L. Jacobo-Albavera, A. Francisco-Balderas, M. Domínguez-Pérez, J. Vazquez Mellado, L. H. Silveira Torre, C. Pineda, G. Martínez-Nava, M. Gutierrez
Journal: Annals of the Rheumatic Diseases (2022)

Background Recent reports have demonstrated that polymorphisms within NLRP3 inflammasome signaling pathway are key factors in the risk to develop some joint inflammatory diseases (1). To date, there is still uncertain information about the presence of these genetic variants and their association with risk of gout. Objectives To determine the association between the single nucleotide polymorphisms (SNPs) within NLRP3 inflammasome genes and the risk of developing gout. Methods We included 220 gout patients and 243 healthy subjects as control group. Clinical examination was performed and laboratory including glucose concentration, total cholesterol and triglycerides were obtained. The frequency and the allelic distribution of eight SNPs from seven different genes within the NLRP3 inflammasome signaling pathway were analyzed using the Step One Plus Real-Time PCR Systems. SNPs were selected by the criterion of minor allele frequency (MAF) (above 1 %), using the 1000 Genomes Project. Genetic variation data for all the SNPs were obtained from the HapMap project ( http://www.hapmap.ncbi.nlm.nih.gov/ ) and the public National Center for Biotechnology Information dbSNP database ( http://www.ncbi.nlm.nih.gov/snp ). The SNPs should not to be in linkage disequilibrium. Ancestry was analyzed using ancestry informative markers differentiating mainly Amerindian, African, and European ancestries. Results The missense SNP rs45520937 in PPARGC1B, showed enhanced association with the risk of developing gout when it was analyzed using the dominant model, evidencing that gout patients carried the A/G-A/A genotype have an elevated risk compared to the control group [OR (95% CI) = 2.30 (1.09-4.86), p=0.030]. While, the adaptor molecule CD14 rs2569190 SNP could be associated with lower risk of gout under an additive model [OR (95 % CI)= 0.41 (0.16-1.05), p= 0.064]. No significant association were identified for the remaining SNPs. Conclusion Our findings suggest that genetic variant rs45520937 of PPARGC1B is significantly associated with the gout susceptibility. References [1]Zhaowen Y, Jin C, Qingrui Y, Yuanchao Z, Lihui H. NLRP3 p.Q705K and CARD8 p.C10X single nucleotide polymorphisms are not associated with susceptibility to rheumatoid arthritis: a meta-analysis. Int J Rheum Dis 2017;20:1481-1491. Acknowledgements Consejo Nacional de Ciencia y Tecnología (CONACYT) Disclosure of Interests None declared
POS1081 SERUM MPO-DNA COMPLEX LEVEL CORRELATES WITH DISEASE ACTIVITY IN PSORIATIC ARTHRITIS
Authors: B. LI, G. LI, Z. Song, Y. Wang, Z. Zhang
Journal: Annals of the Rheumatic Diseases (2022)

Background NETosis has been found to participate in the pathogenesis of many autoimmune diseases, however rarely reported in psoriatic arthritis (PsA). Objectives We aimed to explore the involvement of NETosis in the inflammation of PsA. Methods Serum MPO-DNA complex was detected by a modified enzyme-linked immunosorbent assay (ELISA) and compared among 74 patients with PsA, 58 patients with psoriasis (PsO) and 20 healthy controls. The association of MPO-DNA level with disease activity index at baseline and follow-up was analyzed in PsA patients. Receiver operating characteristic curve was used to evaluate the predictive value of MPO-DNA for treatment response. Results MPO-DNA complex level in serum was significantly increased in PsA/PsO patients compared to healthy controls ( p &lt;0.001). The level of MPO-DNA was positively associated with DAPSA score and its components (including TJC, SJC, PGA, EGA, VAS-pain and CRP, r=0.25-0.409, all p -value&lt;0.05). Serum MPO-DNA level was downregualted at 12-week after treatment compared to baseline ( p =0.022). The decrease of MPO-DNA level was more dramatic in PsA patients who achieved both ACR50 and PASI50 response than those achieving neither of them at 12 weeks ( p =0.023). ROC analysis revealed that the serum MPO-DNA level predicted both ACR50 and PASI50 achievement at week 12 ( p =0.04, 95% CIs 0.56-0.94). Moreover, the baseline MPO-DNA level ( p =0.009, 95% CIs 0.748-1) and change of MPO-DNA at week 12 from baseline ( p =0.004, 95% CIs 0.802-1) were associated with the achievement of both ACR70 and PASI75 response. Conclusion NETosis plays an important role in psoriatic diseases. The level of MPO-DNA complex in serum reflects disease activity. Serum MPO-DNA complex may be a useful biomarker to predict the therapeutic response in PsA. Table 1. Treatment response and changes of serum MPO-DNA of 29 PsA patients. Items Baseline 12 weeks 24weeks TJC, median (IQR) 3(7) 3(4) 2(3.5) SJC, median (IQR) 2(5) 2(2) 1(3) ESR, median (IQR) mm/h 13(15) 8(10) 10(14) CRP, median (IQR) mg/L 3(10.2) † 2.6(3.72) 2.3(3.8) PGA, median (IQR) 40(30) *†† 20(30) †† 10(17.5) EGA, median (IQR) 30(20) †† 20(10) †† 10(20.4) VAS-pain, median (IQR) 30(30) *†† 20(20) †† 10(10) PASI, median (IQR) 2.8(6.2) *† 0.7(1.5) 0.35(1.55) DAPSA, median (IQR) 15(15.1) † 8.4(8.4) 6.15(10.3) MPO-DNA, median (IQR) 0.416(0.615) * 0.231(0.321) - Minimal disease activity, n (%) 4(13.7%) 6(20.6%) 12(41.3%) ACR50, n (%) - 13(44.8%) 15(51.7%) PASI50, n (%) - 14(48.2%) 17(58.6%) ACR70, n (%) - 4(13.7%) 7(24.1%) PASI75, n (%) - 11(37.9%) 14(48.2%) Both ACR50PASI50, n (%) - 8(27.5%) 13(44.8%) Both ACR70PASI75, n (%) - 3(10.3%) 5(17.2%) Figure 1. ROC curves for predictions of treatment achievements at 12 and 24weeks. Disclosure of Interests None declared
AB0051 EVIDENCE OF VERY EARLY CARTILAGE DAMAGE IN EXPERIMENTAL OSTEOARTHRITIS USING SCANNING ELECTRON MICROSCOPY
Authors: V. C. Carneiro Girao-Carmona, M. Marques Bezerra, F. M. Aragão Ximenes Porto, A. C. Matias Dinelly Pinto, R. Nunes, A. M. Costa Vasconcelos Alves, C. Cabral Campello, A. C. Rocha de Melo Leite, G. A. de Castro Brito, F. A. Castro Rocha
Journal: Annals of the Rheumatic Diseases (2022)

Background Early, reproducible, sensitive imaging biomarkers are an unmet need in experimental osteoarthritis (OA) evaluation. Electron microscopy may reveal joint changes prior to soluble biomarkers. Objectives This study describes very early, quantitative, articular cartilage surface damage in posttraumatic experimental OA models allowing determination of disease severity. Methods Mice (5/group) were subjected to anterior cruciate ligament transection (ACLT), ACLT plus meniscectomy (MNCT), as OA models, or sham surgery and sacrificed 3, 7 or 14 days later. Articular cartilage was collected and processed for optical (H&amp;E; Safranin O staining) or scanning electron microscopy (SEM) analysis. Histology was graded using Osteoarthritis Research Society International (OARSI) parameters whereas cartilage thickness, roughness and damage index were evaluated under SEM. Results Optical microscopy did not reveal significantly relevant cartilage changes in OA models vs controls. Femoral and tibial cartilage thickness were significantly reduced in mice subjected to ACLT or MNCT at 7 and 14 days postsurgery (P&lt;0.05). Cartilage roughness was significantly increased in MNCT agroup as early as 3 days postsurgery, as compared to sham and ACLT groups, being sustained up to 14 days in both femoral and tibial extremities. Articular damage index using SEM was more severe at 14 days postsurgery in ACLT and MNCT vs control groups (P&lt;0.05). Conclusion Posttraumatic experimental OA display quantitative cartilage changes at SEM with increased roughness and thickness as early as 3 days post induction. In addition to unravel very early ultrastructural cartilage damage, these changes may be used as early surrogates for joint damage in experimental OA. Disclosure of Interests None declared
AB1502 AWARENESS OF BIOLOGICAL AGENTS RELATED SIDE EFFECTS AMONG INTERNAL MEDICINE RESIDENTS IN A UNIVERSITY HOSPITAL
Authors: M. Oztas, S. Ugurlu
Journal: Annals of the Rheumatic Diseases (2022)

Background Biological agents have become a core component of therapeutic strategies in the last two decades. The number of patients treated with biological agents has been increasing with the expansion of these agents’ indications among rheumatic disorders. Objectives Unfortunately, biological agents have varied side effect profiles, and rheumatic patients with possible side effects are commonly consulted with internal medicine physicians in emergency departments. We surveyed to assess the awareness of biological agents related side effects among internal medicine residents in our university hospital. Methods We conducted a web-based multiple-choice test with 10 questions in total. Monoclonal antibodies (anti-TNF, anti-CD20), anti-cytokines, and JAK inhibitors related side effects and management of these adverse events were assessed. Figure 1 depicted the topics and the correct answer rate of the related questions. Figure 1. The topics and the correct answer rate of the related questions Results A total of 57 responses were collected and analyzed. The mean number of the correct answers was 6,4± 1,5. Fourteen (24,6%) out of the 57 participants scored below 5, whereas 58% of the participants scored ≥6 points. The majority of the participants have correctly answered the anti-TNF, rituximab and tocilizumab-related questions, however, less than half of the participants have accurately answered the anakinra and JAK inhibitors-related questions (Figure 1). Awareness of the JAK inhibitors related zoster reactivation and increased risk of serious cardiovascular events were 35% and 42%, respectively. The approach to the delayed and mild infusion reactions was adequate, however, 33% of the participants accurately approached the severe infusion reaction. Conclusion Our survey suggests that the awareness of biologic agents related side effects among the internal medicine residents is satisfactory. Poorer results were observed especially in JAK inhibitors related side effects and severe infusion reaction management which indicate the educational needs of the residents for these topics. Disclosure of Interests None declared
AB1061 THE ROLE OF PROSTAGLANDIN E2 IN HYPERTROPHIC OSTEOARTHROPATHY AND/OR CLUBBING OF DIFFERENT CAUSES.
Authors: K. Cajiao, H. Florez, A. Monegal, N. Guañabens, P. Peris
Journal: Annals of the Rheumatic Diseases (2022)

Background Hypertrophic osteoarthropathy (HOA) is characterized by several clinical findings, including arthralgia/arthritis, periostosis, and digital clubbing. It can occur as a congenital condition called pachydermoperiostosis, and more commonly, as a secondary manifestation of pulmonary or extrapulmonary diseases or malignancy. Genomic studies support the role of prostaglandin E2 (PGE2) in the pathogenesis of primary HOA, with mutations in the 15-hydroxyprostaglandin dehydrogenase encoding gene resulting in increased PGE2 levels. Objectives To analyse the clinical characteristics, comorbidities, and the potential role of PGE2 in primary and secondary forms of HOA and/or clubbing and also evaluate the clinical evolution of these patients. Methods Eighteen patients (10 men/8 women) aged 15 to 78 years (49,9 ± 15,6) diagnosed with clubbing and/or HOA were attended in our Rheumatology Department over an 11-year period. We reviewed the clinical characteristics of the patients, including associated comorbidities, image findings, bone turnover markers (BTM), and serum and urinary levels of PGE2, among others. Additionally, we evaluated the treatment and the clinical evolution of these subjects. Results Most patients presented associated clinical conditions for HOA and/or clubbing, with only one, the youngest (15 years old), having primary HOA (pachydermoperiostosis). Pulmonary disorders were the most frequent associated conditions, with interstitial lung disease (4 cases), COPD (3 cases), and lung cancer (4 cases) being the most frequent, followed by liver diseases including primary biliary cirrhosis (1 patient), liver cirrhosis (2 patients) and chronic hepatitis C virus (2 patients). All the subjects evaluated (15/18) presented increased urinary PGE2 levels (the highest being observed in primary HOA), with most also presenting increased serum PGE2 values. BTM were evaluated in most subjects (17/18) showing increased values in most (11/17), particularly in PINP and CTx. 4 patients were treated with selective inhibitors of cyclooxygenase-2 (COX-2) presenting, when evaluated, a small decrease in urinary PGE2 titers and partly improving their symptoms, which clearly improved after treating the associated cause when possible. Conclusion In the present series, all subjects with primary or secondary HOA and/or clubbing presented markedly increased PGE2values, particularly in urine, supporting the role of this agent in the etiopathogenesis of this disorder. Pulmonary disorders, including malignancy and liver diseases, constituted the most frequent associated conditions. The use of COX-2 seems to be an effective symptomatic therapeutic approach in this entity. Disclosure of Interests None declared